The objective is the study of intra and intercellular communication and metabolic cooperation, using multichannel microfluorometry in conjunction with the microinjection of fluroescent tracers (e.g. 6-carboxyfluorescein) or metabolites (e.g. glucose-6-P). Recently the emphasis has been on work with metabolites. While the microinjected metabolites are not themselves fluorescent, they lead to transient changes in the reduction-reoxidation of intracellular fluorescent coenzymes (e.g. NAD(P) yields (reversibly) NAD(P)H.) In recent studies, there was no cell-to-cell transfer of metabolites in EL2 cells, normal mouse fibroblasts NCTC 7505A, mouse melanoma HPM 67 and 80% of L cells. 30% of glia CG 787 and glioma MG 251, 25% of transformed rat fibroblasts NCTC 6992 and 70% of well-differentiated mouse melanoma HPM 73 were well-communicant. Occasional weak communication was found in NCTC 6991. In these cell lines the intercellular transit time tau varied from approximately 1 sec. to 30 sec. The current goals are the study of intercellular transfer kinetics and metabolic cooperation, in correlation to intracellular metabolic activity, intra and extracellular ions and the topography of cells within a cluster (e.g. communication to nearest neighbors or more remote cells via intercellular processes). Towards this goal, a recently completed microscopic-optical arrangement allows simultaneous phase observations and rapid multichannel microfluorometry with an option for fluorescence photography for the definition within a cell cluster of a "communication territory" which may be the structural basis for "multicellular integrated states". The role of Ca ions on the kinetics of intercellular communication and metabolic cooperation will be evaluated using a two-injector system for separate microinjections of Ca ion plis and tracers or metabolites. Clusters followed with tracers or metabolites will be retrieved for subsequent electron microscopic studies. Thus the complex of intercommunicating cells will be defined in terms of intercellular transfer kinetics, metabolite exchange and topography of intercellular junctions.